DESCRIPTION (adapted from the application) The purpose of this application is to secure funding for partial salary support for the named P.I. to relieve him from some of the clinical responsibilities that currently provide salary. This would allow more time to perform patient oriented research outlined in this proposal and mentoring post-doctoral fellows at the Center for Human Nutrition (CHN) at the University of Colorado Health Sciences Center (UCHSC). The P.I. is well positioned to serve these roles in that he has a history of clinical research in the area of human obesity, has recently received independent funding for human nutritional studies, and is currently serving as the Associate Director for Research Training at the CHN under the direction of Dr. James Hill. The presence of the General Clinical Research Center (GCRC), the Clinical Nutrition Research Unit (CNRU), and the CHN have made the UCHSC an exciting institution for obesity related research and has attracted a large number of excellent post-doctoral fellows but there is a need/opportunity for a mid [sic] career MD to help with the mentoring load. This award would solidify the candidate in this role at an important time for him and the CHN. The proposed research examines the hypothesis that as compared to individuals predisposed to weight gain, lean individuals more accurately sense and respond metabolically and behaviorally to positive energy balance. It is hypothesized that as compared to reduced obese, lean individuals will respond to a period of positive energy balance with a reduction [sic] the oxidation of glucose (insulin resistance), an increase in the oxidation of dietary fat by skeletal muscle, and a decreased drive to eat. The result of these differences in fuel metabolism are that lean individuals will more effectively defend against a state of positive fat balance as compared to reduced obese. To test these ideas lean and reduced obese individuals will be studied following 3-days of overfeeding. 1. Euglycemic clamps will be performed to examine insulin sensitivity, 2. meal studies will be performed examining the metabolic fate of labeled fat and carbohydrate included in a test meal, and 3. Hunger, satiety, and palatability will be measured during and following hypercaloric feeding. Indirect calorimetry, tracer oxidation, limb balance, and sampling of skeletal muscle and adipose tissue are proposed to give a more complete view of meal associated nutrient metabolism in these two groups. These studies will provide insight into the biology that predisposes to weight regain following weight reduction and will lay the groundwork for future studies of the abnormalities in nutrient metabolism that exist in obese and pre-obese individuals.